Institute of Cardiovascular Science, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Laboratory Animal Center, Xi'an Jiaotong University, Xi'an, China.
Animal Model Exp Med. 2022 Feb;5(1):72-80. doi: 10.1002/ame2.12197. Epub 2021 Dec 7.
Porcine pancreatic elastase (PPE) is successfully used to induce abdominal aortic aneurysm (AAA) in mice. However, differences between mouse strains in susceptibility to PPE induction have been reported. Kunming mouse is one of the most frequently used strains in China but whether it is suitable for induction of AAA by PPE application remains unclear.
PPE infusion (1.5 units/ml) in temporary controlled aorta was performed to induce AAAs in both C57BL/6J and Kunming mice. Phosphate-buffered saline (PBS) application was used as vehicle control. The aorta diameters of all mice were measured at days 0 and 14 after surgery to evaluate the AAA formation.
After 14 days of PPE or PBS infusion, all mice were sacrificed and aorta tissues were collected for histological staining analysis. At the 14th day after infusion, PPE successfully induced aortic dilation in Kunming mice and typical AAA in C57BL/6J mice. The aorta diameter increased by 0.23 mm in Kunming mice after PPE infusion, while it was 0.72 mm in the C57BL/6J strain. PPE induced mild elastin degradation, smooth muscle cell (SMC) depletion and mural leucocyte infiltration in Kunming mice, but in PPE-sensitive C57BL/6J mice, it induced total loss of SMCs, elastin disappearance and diffused infiltrated leucocytes in aortic aneurysmal segments. The effects of PPE in inducing angiogenesis and upregulating matrix metalloproteinase 2 and 9 expression in Kunming mice were also weaker than that in C57BL/6J mice.
At the reported dose of PPE, Kunming mouse is not as susceptible to AAA formation as C57BL/6J mice. The failure of PPE to induce AAA formation in Kunming mice may be associated to its inability to boost a strong inflammatory response.
猪胰腺弹性蛋白酶（PPE）成功地用于诱导小鼠腹主动脉瘤（AAA）。然而，不同品系的小鼠对 PPE 诱导的敏感性存在差异。昆明小鼠是中国最常用的品系之一，但它是否适合应用 PPE 诱导 AAA 尚不清楚。
采用临时控制主动脉内 PPE 输注（1.5 单位/ml）的方法诱导 C57BL/6J 和昆明小鼠发生 AAA。应用磷酸盐缓冲液（PBS）作为载体对照。术后第 0 天和第 14 天测量所有小鼠的主动脉直径，以评估 AAA 的形成。
PPE 或 PBS 输注 14 天后，处死所有小鼠，采集主动脉组织进行组织学染色分析。输注后第 14 天，PPE 成功诱导昆明小鼠主动脉扩张，C57BL/6J 小鼠发生典型 AAA。PPE 输注后，昆明小鼠的主动脉直径增加了 0.23mm，而 C57BL/6J 品系的直径增加了 0.72mm。PPE 诱导昆明小鼠轻度弹性蛋白降解、平滑肌细胞（SMC）耗竭和壁层白细胞浸润，但在 PPE 敏感的 C57BL/6J 小鼠中，它诱导 SMC 完全丢失、弹性蛋白消失和弥漫性浸润的白细胞在主动脉瘤段。PPE 在诱导血管生成和上调基质金属蛋白酶 2 和 9 表达方面的作用在昆明小鼠中也弱于 C57BL/6J 小鼠。
在报告的 PPE 剂量下，昆明小鼠对 AAA 形成的敏感性不如 C57BL/6J 小鼠。PPE 未能在昆明小鼠中诱导 AAA 形成可能与其不能增强强烈的炎症反应有关。
